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Multi‐site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical‐based studies. A multi‐site dataset of 216 Parkinson's disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE‐p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site‐effects quantitatively and allow the harmonization of data. This method is user‐friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites. We propose a method to harmonize MRI multi‐center data using the predictive probabilities from Gaussian Process site classification. These parameters encode quantitatively site‐effect differences and can be used as Weighted Harmonization Parameters (WHARMPA). This method is user‐friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites.

Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

Subtyping of ketoacidosis, a metabolic state characterized by blood acidification due to various causes, remains challenging in forensic casework. Postmortem omics samples paired with machine learning offer an independent tool to address this challenge. However, such data, especially related to real forensic cases, are rare. In Sweden, high-resolution mass spectrometry data routinely collected in forensic toxicology, can be leveraged for metabolomic analysis. Here, we integrate postmortem metabolomics and machine learning models to detect and subtype ketoacidosis-related deaths using real forensic cases in Sweden. From femoral blood samples of 109 alcoholic ketoacidosis cases, 220 diabetic ketoacidosis cases, 140 hypothermia cases, and 1,229 controls (hanging cases), we developed and tested three machine learning models, which achieved over 90% accuracy in ketoacidosis detection and over 80% in subtyping. Validation with independent cohorts (21 starvation cases, 29 alcoholic controls, and 40 diabetic controls) confirmed robustness with over 80% of starvation cases classified as ketoacidosis-related. Feature clustering highlighted metabolites such as cortisol to be important for subtyping. In summary, our findings demonstrate that combining machine learning with postmortem metabolomics enables accurate detection and subtyping of ketoacidosis-related deaths, which is useful for forensic casework.

Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain. Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task. No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls. Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function.

BACKGROUND: The rat lungworm Angiostrongylus cantonensis can cause eosinophilic meningoencephalitis in humans. This nematode’s main definitive hosts are rodents and its intermediate hosts are snails. This parasite was first described in China and currently is dispersed across several Pacific islands, Asia, Australia, Africa, some Caribbean islands and most recently in the Americas. Here, we report the genetic variability among A. cantonensis isolates from different geographical locations in Brazil using mitochondrial cytochrome c oxidase subunit I (COI) gene sequences. METHODS: The isolates of A. cantonensis were obtained from distinct geographical locations of Brazil. Genomic DNAs were extracted, amplified by polymerase reaction, purified and sequenced. A partial sequence of COI gene was determined to assess their phylogenetic relationship. RESULTS: The sequences of A. cantonensis were monophyletic. We identified a distinct clade that included all isolates of A. cantonensis from Brazil and Asia based on eight distinct haplotypes (ac1, ac2, ac3, ac4, ac5, ac6, ac7 and ac8) from a previous study. Interestingly, the Brazilian haplotype ac5 is clustered with isolates from Japan, and the Brazilian haplotype ac8 from Rio de Janeiro, São Paulo, Pará and Pernambuco states formed a distinct clade. There is a divergent Brazilian haplotype, which we named ac9, closely related to Chinese haplotype ac6 and Japanese haplotype ac7. CONCLUSION: The genetic variation observed among Brazilian isolates supports the hypothesis that the appearance of A. cantonensis in Brazil is likely a result of multiple introductions of parasite-carrying rats, transported on ships due to active commerce with Africa and Asia during the European colonization period. The rapid spread of the intermediate host, Achatina fulica, also seems to have contributed to the dispersion of this parasite and the infection of the definitive host in different Brazilian regions.

Because many patients who have swallowed foreign bodies are asymptomatic, physicians must maintain a high index of suspicion. The majority of ingested foreign bodies pass spontaneously, but serious complications, such as bowel perforation and obstruction, can occur. Foreign bodies lodged in the esophagus should be removed endoscopically, but some small, blunt objects may be pulled out using a Foley catheter or pushed into the stomach using bougienage [corrected] Once they are past the esophagus, large or sharp foreign bodies should be removed if reachable by endoscope. Small, smooth objects and all objects that have passed the duodenal sweep should be managed conservatively by radiographic surveillance and inspection of stool. Endoscopic or surgical intervention is indicated if significant symptoms develop or if the object fails to progress through the gastrointestinal tract.

Objective This research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID‐19). Methods COVID‐19 patients were evaluated using T1‐weighted and diffusion tensor imaging (DTI) on a 3T MRI scanner, 9.94 ± 3.83 months after COVID‐19 diagnosis. Gray matter (GM) voxel‐based morphometry was performed using FSL‐VBM. Voxelwise statistical analysis of the fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was carried out with the tract‐based spatial statistics in the olfactory system. The smell identification test (UPSIT) was used to classify patients as normal olfaction or olfactory dysfunction groups. Intergroup comparisons between GM and DTI measures were computed, as well as correlations with the UPSIT scores. Results Forty‐eight COVID‐19 patients were included in the study. Twenty‐three were classified as olfactory dysfunction, and 25 as normal olfaction. The olfactory dysfunction group had lower GM volume in a cluster involving the left amygdala, insular cortex, parahippocampal gyrus, frontal superior and inferior orbital gyri, gyrus rectus, olfactory cortex, caudate, and putamen. This group also showed higher MD values in the genu of the corpus callosum, the orbitofrontal area, the anterior thalamic radiation, and the forceps minor; and higher RD values in the anterior corona radiata, the genu of the corpus callosum, and uncinate fasciculus compared with the normal olfaction group. The UPSIT scores for the whole sample were negatively associated with both MD and RD values (p‐value ≤0.05 FWE‐corrected). Interpretation There is decreased GM volume and increased MD in olfactory‐related regions explaining prolonged olfactory deficits in post‐acute COVID‐19 patients.

Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 ( ADGRL3 ; formerly latrophilin 3, LPHN3 ) is associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of ADGRL3 risk variants. We examined here whether individuals with different ADGRL3 haplotypes, including both patients with ADHD and healthy controls, showed differences in brain anatomy and function. We recruited and genotyped adult patients with combined type ADHD and healthy controls to achieve a sample balanced for age, sex, premorbid IQ, and three ADGRL3 haplotype groups (risk, protective, and others). The final sample (n = 128) underwent structural and functional brain imaging (voxel-based morphometry and n-back working memory fMRI). We analyzed the brain structural and functional effects of ADHD, haplotypes, and their interaction, covarying for age, sex, and medication. Individuals (patients or controls) with the protective haplotype showed strong, widespread hypo-activation in the frontal cortex extending to inferior temporal and fusiform gyri. Individuals (patients or controls) with the risk haplotype also showed hypo-activation, more focused in the right temporal cortex. Patients showed parietal hyper-activation. Disorder-haplotype interactions, as well as structural findings, were not statistically significant. To sum up, both protective and risk ADGRL3 haplotypes are associated with substantial brain hypo-activation during working memory tasks, stressing this gene’s relevance in cognitive brain function. Conversely, we did not find brain effects of the interactions between adult ADHD and ADGRL3 haplotypes.

Vegetable trimmings can be used to stabilize edible O/W Pickering emulsions. The lignocellulosic biomass (LCB) from the leek trimmings was mechanically treated to produce high-yield lignocellulose micro and nanofibrils (LCF) using a high-pressure homogenizer (HPH). Different O/W phase ratios (20/80, 30/70, and 40/60 wt.%) were studied. The use of the micro/nano cellulosic fibers increased the stabilization of the Pickering emulsions by 30–40%. In all cases, stable emulsions were obtained, with emulsification indexes > 92%. The respective stabilization mechanism was thoroughly analysed from confocal laser scanning, and cryo-scanning electron microscopy, which showed the fibers are not coating the droplets but forming a network that traps the droplets and prevents coalescence. The most stable batch formulations, O/W 30/70 wt.% (LCB 4.2 wt.%) and O/W 40/60 wt.% (LCB 3.6 wt.%), were also studied in continuous mode using NETmix technology. Results show the scale-up feasibility of the production of Pickering emulsions containing LCF. Most significantly, this work proposes a continuous process to produce Pickering emulsions stabilized with a natural biopolymer extracted from leek trimmings, which is suitable to industrial manufacturing processes. This valorizes the vegetable trimmings that are usually tossed away as waste, creating new market niches and business models based on circular economy concepts.

Objective: To determine whether oral vitamin D supplementation reduces the risk of glucocorticoid (GC)-associated severe adverse events (SAEs) in patients with giant cell arteritis (GCA) included in the Spanish ARTESER registry. Methods: The ARTESER registry collected data from patients diagnosed with GCA across 26 Spanish public hospitals between June 2013 and March 2019. SAEs were defined as fatal, life-threatening, or requiring hospitalization. Patients were categorized according to the use or non-use of oral vitamin D supplements. Incidence rates (IRs) of SAEs were expressed per person-year with 95% confidence intervals (CIs). Cox proportional hazards models assessed vitamin D supplementation and its interaction with cumulative glucocorticoid dose. Results: Of 1568 patients (mean age 76.9 ± 8.1 years; 70.1% women) receiving GC, 120 (7.6%) experienced SAEs (IR 0.039; 95% CI 0.033–0.047). Vitamin D supplementation was documented in 1186 (75.6%) compared with 382 (24.4%) non-supplemented patients. SAE incidence was similar in supplemented (n = 89; 7.5%; IR 0.038, 95% CI 0.030–0.046) and non-supplemented patients (n = 31; 8.1%; IR 0.045, 95% CI 0.031–0.064) (p = 0.387). Multivariable Cox regression showed a significant interaction between vitamin D supplementation and cumulative glucocorticoid dose (interaction term HR 0.90; p = 0.033), consistent with a dose-dependent protective effect. Conclusions: Vitamin D supplementation was not independently associated with a lower incidence of GC-related SAEs, likely due to residual confounding factors. However, the interaction with cumulative GC exposure suggests a modulatory effect. Prospective studies incorporating stratified baseline vitamin D assessments are warranted.